ERCC2／XPD 和 XRCC1基因多态性与食管癌铂类药物化疗敏感性的关系

摘要

Objective:To evaluate the relationship of DNA repair gene ERCC2 /XPD and XRCC1 polymorphisms with chemosensitivity to platinum -based chemotherapy in advanced esophageal squamous cell carcinoma.Methods:ERCC2 /XPD Lys751Gln and XRCC1 Arg399Gln gene polymorphisms were detectd by the polymerase chain reaction-restriction fragment length polymorphism (PCR -RFLP)assays in 80 patients with advanced esophageal squamous cell carcinoma who received platinum -based chemotherapy.Unconditional logistic regression model was used to ana-lyze the assoc iation between ERCC2 /XPD and XRCC1 gene polymorphisms and chemosensitivity.Results:The fre-quency for ERCC2 /XPD 751 genes Lys /Lys,Lys /Gln,Gln /Gln genotypes were 5 8 cases (72 .5 %),17 cases (21.3%)and 5 cases(6.3%)and XRCC1 399 genes Arg/Arg,Arg/Gln,Gln/Gln genotypes frequencies were 43 cases(53.8%),28 cases(35.0%)and 9 cases(11.3%).The overall response rate was 52.5%,including 29 cases with partial reponse,23 cases with stable disease,and 28 cases with progression disease.ERCC2 /XPD gene polymor-phisms correlated with sensitivity to chemotherapy(OR =3.723,95%CI =1.613 ~12.532,P <0.01).The XRCC1 399Arg allele carriers had higher chemosensitivity to platinum than the cases presenting with Gln/Gln genotype (OR =3.62,95%CI =1.19 ~11.43,P <0.01).Conclusion:ERCC2 /XPD and XRCC1gene polymorph isms may be associated with chemosensitivity to platinum -based chemotherapy in advanced esophageal carcinoma.%目的：研究着色性干皮病基因（ERCC2／XPD）和 X 线修复交叉互补基因1（XRCC1）单核苷酸多态性与晚期食管癌铂类药物化疗敏感性关系。方法：采用聚合酶链反应－限制性片段长度多态性（PCR －RFLP）方法检测80例以铂类药物为主要化疗方案的食管癌患者和 CC2／XPD Lys751Gln 和 XRCC1 Arg399Gln 基因多态性，应用非条件 Logistic 回归计算 OR 值及95％CI，分析不同基因型与化疗疗效的关系。结果：80例晚期食管癌患者中，ERCC2／XPD 751基因 Lys／Lys、Lys／Gln、Gln／Gln 基因型的分布频率分别为58例（72．5％）、17例（21．3％）和5例（6．3％）；XRCC1399基因 Arg ／Arg、Arg ／Gln、Gln ／Gln 基因型的分布频率分别为43例（53．8％）、28例（35．0％）和9例（11．3％）；化疗后临床获益率为52．5％，其中完全缓解（CR）、部分缓解（PR）、稳定（SD）和进展（PD）患者分别为0例、29例（36．3％）、23例（28．8％）和28例（35．0％），ERCC2／XPD 基因型多态性与化疗敏感性具有相关性（OR ＝3．723，95％CI ＝1．613～12．532，P ＜0．01）；发现至少携带1个 XRCC1399Arg 等位基因型患者的化疗敏感性是 Gln ／Gln 基因型的3．62倍（校正 OR ＝3．62，95％CI＝1．19～11．43，P ＜0．01）。结论：ERCC2／XPD 和 XRCC1基因多态性可能与晚期食管癌铂类药物化疗敏感性有一定关系。